# Targeted Imaging of Fibrosis in the Left Atrium

> **NIH NIH R44** · COLLAGEN MEDICAL, LLC · 2021 · $766,000

## Abstract

Abstract
Significance: Atrial fibrosis plays a central role in the development of atrial fibrillation (AF) and heart failure,
which are both common conditions in the elderly and associated with significant morbidity and mortality. This
proposal addresses an unmet diagnostic need for non-invasive methods to characterize atrial fibrosis through
non-invasive molecular imaging of type 1 collagen, the hallmark pathology of atrial fibrosis. Hypothesis: We
hypothesize that a collagen-binding gadolinium chelate will localize in fibrotic atrial tissue, thus enabling
targeted molecular imaging of atrial fibrosis to be performed with a high degree of accuracy. Preliminary data:
The affinity and specificity of Collagen Medical’s proprietary probe CM-101 for type 1 collagen are well
established. Our preliminary efficacy data have established that CM-101 can quantify fibrosis burden in a rat
bile duct ligation model (BDL) of chronic liver disease. Additionally, CM-101 enhanced differences in T1 and
signal intensity in a canine myocardial infarct model were shown to be related to the fibrosis burden in the left
ventricle. Here, for the first time, we propose to use the agent to image left atrial fibrosis using a porcine model
of atrial fibrillation. Specific Aims: In Phase 1, Specific Aim 1, of this Fast Track proposal we aim to establish
that CM-101 specifically accumulates in regions of atrial fibrosis as compared with a non-targeted control and
that it can be imaged in vivo with T1 weighted sequences. A porcine model of focal left atrial fibrosis created
using radiofrequency ablation catheters will be used. The gating decision criteria for a transition to Phase 2 are
based on quantitative assessment of tissue specificity vs. non-targeted control and in vivo imaging. In Phase
2, Specific Aim 2 of the grant, we will demonstrate the ability of CM-101 enhanced MRI to quantify patchy and
diffuse left atrial fibrosis in a porcine model of atrial fibrillation and will compare the collagen targeted agent to
the current gold standard, late gadolinium enhancement (LGE) using the non-targeted agent (Gd-DOTA).
Overall Impact: We anticipate that the targeted and specific nature of CM-101 will produce significantly more
accurate data than LGE using non-targeted chelates, the current gold standard. Together, data obtained in
these studies will support an IND application and accelerate translation into the clinical realm.

## Key facts

- **NIH application ID:** 10384068
- **Project number:** 4R44AG059524-02
- **Recipient organization:** COLLAGEN MEDICAL, LLC
- **Principal Investigator:** Valerie Humblet
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $766,000
- **Award type:** 4N
- **Project period:** 2018-08-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10384068

## Citation

> US National Institutes of Health, RePORTER application 10384068, Targeted Imaging of Fibrosis in the Left Atrium (4R44AG059524-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10384068. Licensed CC0.

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